The long-term goal of this project is to study the effectiveness of a controlled antibiotic relasing-prosthetic heart valve in preventing post-operative occurrences of prosthetic heart valve endocarditis and the devastating consequences of this infectious disease in prosthetic heart valve recipients. To assess its therapeutic potential, the antibiontic-releasing prosthetic heart valve is being extensively evaluated in a series of experimental models of prosthetic valve endocarditis in dogs. Addititional experiments are being performed in an effort to investigate the relationship between the establishment of acute infections and thrombus formation in prosthetic heart valves and vascular prostheses. Predictions derived from compartmental pharmacokenetic modeling, employing the predetermined in vitro diffusion rate constants of gentamicin from the prosthetic heart valves, are being compared to actual drug serum level determinations obtained in the implantation studies with the drug-loaded prosthetic heart valves in dogs. The modeling studies will provide a better understanding of the in vivo performance of such drug delivery systems especially in cases where drugs of known toxicity are employed.